Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity

• Published in: Journal of immunology research Vol. 2019; no. 2019; pp. 1 - 7
• Main Authors: Lin, Chiou-Feng, Tseng, Po-Chun, Chen, Chia-Ling, Wang, Yun-Ting, Lee, Yuarn-Jang, Liu, Yung-Ching, Krisnawati, Dyah Ika, Shen, Ting-Jing
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2019; Hindawi; John Wiley & Sons, Inc; Wiley
• Subjects: Antibodies, Blocking - immunology; Antibodies, Blocking - metabolism; Antibodies, Blocking - pharmacology; Antimicrobial agents; Autoantibodies; Autoantibodies - immunology; Autoantibodies - pharmacology; Autophagy; Bacterial infections; Biodegradation; Biomarkers; Case-Control Studies; Chemokines; Cytokines; Cytokines - metabolism; Defects; HIV; Host-Pathogen Interactions - drug effects; Host-Pathogen Interactions - immunology; Human immunodeficiency virus; Humans; Immunity, Innate; Immunodeficiency; Immunology; Immunomodulation; Immunosurveillance; Infections; Inflammation; Innate immunity; Interferon; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - immunology; Laboratories; Macrophage Activation; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Monocytes; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Pathogens; Phagocytosis; Phagocytosis - immunology; Reactive nitrogen species; Reactive oxygen species; Reactive Oxygen Species - metabolism; THP-1 Cells; Tuberculosis; γ-Interferon
• ISSN: 2314-8861; 2314-7156; 2314-7156
• DOI: 10.1155/2019/1629258

The interferon- (IFN-) γ expression is elicited in response to microbial infections and activates immune surveillance by antimicrobial immune elements to induce microbial killing. Patients with adult-onset immunodeficiency who suffer from recurrent infections with microbes, particularly nontuberculous mycobacteria (NTM), commonly display genetic defects in IFN-γ signaling as well as the generation of anti-IFN-γ autoantibodies (autoAbs). Because IFN-γ is an activator of macrophage differentiation and a proinflammatory activator of innate immunity, the blockade effects of the autoAbs present in NTM patient serum on IFN-γ are hypothesized to regulate the antimicrobial function of macrophages. In the presence of patient serum, IFN-γ-induced type 1 macrophage (M1) differentiation was inhibited in PMA-stimulated human monocytic THP-1 cells. Treatment with patient serum significantly blocked the production of proinflammatory factors, including cytokines/chemokines and reactive oxygen/nitrogen species, by M1 macrophages. Importantly, IFN-γ-facilitated phagocytosis and degradation of heat-killed mycobacterium were decreased by cotreatment with patient serum. These results show the blockade activity of anti-IFN-γ autoAbs on IFN-γ-mediated antimicrobial immunity in macrophages.